1. Field of the Invention
The invention relates to the field of implantable drug delivery systems, specifically to a remotely activated piezoelectric pump for the controlled delivery of biological agents to the disc space and spine.
2. Description of the Prior Art
Scientists and spinal surgeons have demonstrated that a genetically produced protein, recombinant human bone morphogenetic protein-2, or rhBMP-2, has the ability to stimulate a patient's own cells to make more bone. This finding has obvious beneficial implications for the treatment of many bone fractures and bone defects. More importantly, though, rhBMP-2 can be tremendously beneficial to patients undergoing spinal fusion. RhBMP-2 will eliminate the need for bone transplantation from the pelvis. It may also more reliably and more quickly produce fusion of spinal vertebrae. It may even reduce the need for the implantation of spinal rods and screws.
Back pain is one of the 15 most commonly treated medical conditions in the United States today and is second only to the common cold as the most common reason for physician visits. Back pain not only has a profound effect on patients, it has an exceedingly high societal cost. Back pain is the second most common cause of lost productive time of the pain disorders and results in the largest amount of total lost time. It has been stated that of all medical conditions, back pain results in the most lost productivity. It is estimated that the direct and indirect costs associated with the disorder are approximately 50 billion dollars per year in the United States alone. Although back pain is multifactorial, degenerative disc disease is often involved in the pathogenesis and subsequent propagation of lower back pain. The disc space is composed of disc and surrounding annulus fibrosus. As the disc degenerates hypertrophy is increased in order to support the body weight, eventually leading to back pain.
The achievement of a bony fusion is necessary for bony regeneration and healing, and is crucial to the success of many orthopedic procedures. In the spine alone, it is estimated that more than 300,000 spinal fusion procedures are performed each year in the United States.
Traditionally, spinal fusions have been performed by decorticating the host bone, and laying down autograft from the iliac crest to achieve a bony “in-situ” fusion. With the advent and popularity of instrumentation for spinal fusions (i.e. pedicle screws), adjacent segments could now be held together, immobilizing them, thus enhancing the fusion rate. However, even with the use of iliac crest autograft and spinal fixation, the development of a biologic fusion—i.e., new bone formation at the fusion site, is not consistent. Spinal fixation allows for short term mechanical stabilization, but lacks the capacity to produce a consistent biologic fusion. Iliac crest autografts have associated morbidities related to the harvesting, including pain at the donor site. Moreover, the consistency of the bone harvested is dependent on patient's intrinsic bone quality and the surgeon's ability to harvest a significant amount of bone needed for a bony fusion. The need for a bone graft substitute that can consistently lead to bony fusions without the need for iliac crest autografts has resulted in the production of bone graft substitutes, such as demineralized bone matrix (DBM). DBM is a bone graft extender, made of allograft, which has the capacity to be osteoconductive, that is, serve as a bridge between two bone chips to facilitate a fusion. DBM, however, is not capable of forming new bone (osteoinductive).
The commercialization of recombinant human bone morphogenetic protein-2 (BMP-2) has lead to a product that has osteoinductive properties that may be used to consistently produce a bony fusion. Currently, BMP-2 is FDA approved as a replacement for autograft in anterior lumbar interbody fusion (ALIF) using an anterior cage. It is marketed as INFUSE Bone Graft by Medtronics, Inc. INFUSE is made up of recombinant BMP-2 and absorbable collagen sponge (ACS; from bovine Achilles tendon). In a typical operation, BMP-2 is added to the ACS for a minimum of 15 minutes prior to implantation to ensure adequate binding of BMP-2. Once added to ACS, the BMP-2 must be used within 2 hours. The mean residence time of BMP-2 after implantation has been measured in a rat femoral onlay model implantation model to be 7.8 days. The maximum level of BMP-2 detected in the circulation was 0.1% of the implanted dose after six hours. In a rat long bone ectopic implant model, the mean residence time ranged from 3.6 to 4.6 days (McKay—p. 72). In human patients, BMP-2 is estimated to be present at the implant site for 3-4 weeks, and is cleared from the blood by the liver and excreted via the urine. Histology from animal models suggests that the ACS is reabsorbed in 4-12 weeks.
Although BMP-2 is only FDA approved for anterior lumbar fusions, it has already been used in many different types of spinal fusion surgeries, including posterolateral fusions, and anterior cervical fusions. The posterolateral fusions appear to be effective with BMP-2 (although there was concern that it may actually work too well, and cause spinal stenosis). The anterior cervical fusions were effective from the standpoint of cervical fusions, but often induced tracheal-esophageal swelling, leading to emergency intubations in some patients. BMP-2 for human bones is used at the concentration of 1.5 mg BMP-2 per 1 cc of solution. In a typical anterior lumbar fusion, the cage is filled with 4 cc of collagen sponge, saturated with 4 cc of the 1.5 mg/cc BMP-2 solution.
The current limitations of the BMP-2 technology are as follows:
i) BMP-2 is soaked into a collagen sponge. When the sponge is implanted, any squeezing or manipulation of the sponge results in loss of BMP-2, making the delivery technique inefficient. ii) BMP-2 half-life and time in circulation is short, usually less than a week, and an average fusion takes 3-6 months to complete. iii) Current BMP-2 has to be delivered at massive quantities compared to what is actually needed (milligram doses, as opposed to nanogram or microgram doses of what is needed), costing health insurance and consumers up to $8,000 to $10,000 per implant. Moreover, increased amounts of BMP-2 placed in the cervical or lumbar spine can lead to a tremendous amount of swelling. iv) BMP-2 delivery is not well directed, and is only passively absorbed. As a result, BMP-2 placed posterolaterally has the potential of fusing too much, leading to spinal stenosis. BMP-2 placed in the anterior cervical spine leads to swelling, from the BMP-2 passively leaking into the adjacent soft tissue. v) Fusion is established purely via a radiographic impression of bone formation via x-rays or CT-scan. No physiological monitoring of motion is placed to establish that a fusion has been established.
The infusion of growth factors to the intervertebral disc has been explored by various authors in the prior art. All the infusions, however, have been via direct one time infusions, or in experimental models via an external catheter.
What is needed is a method and apparatus that provides continuous infusion of various growth factors into the disc space to preserve it, instead of removing and fusing it in order to alleviate the thousands of patients currently suffering from chronic low back pain.